Sleepless and Sleepy: 50 Challenging Sleep Medicine Cases [1 ed.] 3031183738, 9783031183737, 9783031183744

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Sleepless and Sleepy 50 Challenging Sleep Medicine Cases Alcibiades J. Rodriguez Editor

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Sleepless and Sleepy

Alcibiades J. Rodriguez Editor

Sleepless and Sleepy

50 Challenging Sleep Medicine Cases

Editor Alcibiades J. Rodriguez, MD, FAASM Medical Director, NYU Langone Comprehensive Epilepsy Center-Sleep Center Director, Neurology Sleep Medicine Associate Professor of Neurology NYU Grossman School of Medicine New York, NY, USA

ISBN 978-3-031-18373-7    ISBN 978-3-031-18374-4 (eBook) https://doi.org/10.1007/978-3-031-18374-4 © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

To my mother Flora and father Alcibiades, whose teachings of hard work, discipline, and love made me a better person and professional.

Foreword

Teaching the art and science of medicine is a difficult and fundamental task with the goal of sharing clinical experience with students. This transmission of knowledge can be done in different forms, from conventional lectures to focused seminars, activities that need to be complemented with individual work with good teaching material. An excellent way to promote this learning process is also sharing selected clinical cases with students in the form they were experienced by their doctors in real life. This usually starts with the patient complaints and relevant clinical questions, follows with the physical examination and the differential diagnoses, continues with the ancillary tests results and ends with a final interpretation of all the findings with a diagnosis and management plan. To reflect all this process in a case presentation requires excellent teaching material shown in an appropriate way by experienced authors. I think this has been achieved in this book, which contains 50 sleep medicine teaching cases written by their physicians as they were experienced in their practice. They refer to adult and pediatric patients with common and unusual sleep medicine problems that clinicians have seen in their professional activity and were selected by their specific learning value. Authors are experienced sleep medicine clinicians from all over the world, coordinated by the editor of this book, Dr (Prof) Alcibiades Rodriguez. Dr(Prof) Alcibiades Rodriguez—a former Mayo Clinic Fellow in Sleep Medicine and currently Director, Neurology Sleep Medicine, and Associate Professor of Neurology at New York University School of Medicine—has assembled the book by selecting the contributors and topics, editing the chapters, and organizing the final version of this book. His ample clinical experience in sleep disorders has allowed him to give the book the flavor of real daytime sleep clinics. It has been my pleasure to know Prof Alcibiades Rodriguez for the last 10 years, as we both are teachers in a yearly seminar in Sleep Medicine organized in the Monastery of Les Avellanes, in Lleida, Spain. I have had the opportunity to enjoy his teaching abilities both in lecturing and particularly interviewing sleep medicine patients, an activity which has allowed many students to learn how to face a patient with sleep disorder.

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Foreword

I think the book may be an important aid for students, fellows, and doctors interested in sleep medicine and hope readers will find attractive the combination of solid scientific evidence with entertaining real-life experiences as is presented here. 

Dr. Joan Santamaria Emeritus Consultant and Researcher Hospital Clínic of Barcelona Barcelona, Catalonia, Spain

Preface

It was some years ago during my clinical rotation at the National Hospital for Neurology and Neurosurgery at Queen’s Square, London, UK, that I decided to pursue an epilepsy, and later by extension, a sleep medicine career. The Grand Rounds performed there impressed me. During these rounds, actual patients were interviewed and examined in front of students, registrars (fellows), and seasoned neurologists. This experience had a long-lasting impact on me. It was then that I discovered the book Fifty cases from the National Hospital, which was based on these Grand Rounds. I became fascinated with the diversity and complexity of the cases presented at this venerable institution. I read that book ­several times, case by case, to study for my certification and re-certifications boards and later, to review my general neurology knowledge. Later, during my neurology training at Tufts University in Boston, MA, we also presented difficult and demanding cases to senior physicians, which as trainees we encountered in our clinical rotations. I have also been privileged to participate in the annual seminars in Sleep Medicine, organized by the Spain Neurological Society and the sleep-wake working group in Lleida, Cataluña, Spain. During these sessions, we witness sleep tests, in actual patients, being conducted at the Hospital Clínic of Barcelona and have the opportunity to interview them remotely. The last day, patients are brought in from the community and different specialists take turns to interview, examine, and, later, discuss the cases with the trainees. Now, I find myself face to face with my past, paying tribute to all those influential experiences with a collection of cases of my own sleep medicine profession. This long-waited project aims to show the heterogeneous, unique, and challenging cases that we encounter in sleep medicine every day. There are cases from different parts of the world, adults and pediatrics, some pulmonary, some more neurological/psychiatric, and some more surgically o­ riented, but sharing the same sleep medicine language. It will be useful to residents, sleep medicine fellows, and full-time sleep and non-sleep professionals to sit and read one or two cases at a time, especially to the young professionals starting their journey within this wonderful specialty. Some cases are classic, some are not, some combine other specialties, and some are just related to sleep in different ways.

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Preface

Some have a definite answer and some only time will tell their true nature. Let me introduce to you these 50 cases, hoping you enjoy the experience, just as much as I did reading, editing, and learning from them. New York, NY March 2022

Alcibiades J. Rodriguez

Acknowledgments

This book has been possible due to the contribution of many. Throughout my career, I have met people from all over the world, students, residents, fellows, colleagues, and teachers, some of them have become friends. Thank you all the contributors for your incredible help, for the outstanding and amazing cases that appear in this book, and for tolerating my multiple requests, questions, and demands. To my dear colleagues at NYU Langone Medical Center, who helped with their expertise to review cases, videos, and illustrations for clarity, I would like to express my deepest gratitude. I want to thank all the staff at the NYU Langone Comprehensive Epilepsy Center-Sleep Center, my home away from home. To my secretaries, who protected my time to work on this project; nighttime technicians, who take care of patients; and especially to my daytime technicians for their effort in obtaining the correct figures and video editing for several cases. It has been many years growing together. Finally, to the patients themselves for teaching all of us something new every single day. In my life, I have learned from them all.

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Dear Sir or Madam, will you read my book? It took me years to write, will you take a look? Paperback writer John Lennon/Paul McCartney, 1966

Contents

1

 Case 1. The Borderlands of Sleep-Wake Movements and Epilepsy������   1 Hernando Pérez Díaz and Juan Jesús Rodríguez Uranga

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 Case 2. Sometimes Lightheadedness a Harbinger����������������������������������   7 Susan Muraida and Madeleine Grigg-Damberger

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 Case 3. Testosterone and Gender: Not What You Think������������������������  13 Jordan C. Stern

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Case 4. “Despite of CPAP Therapy, My Husband Still Has a Disturbed Nocturnal Sleep” ��������������������������������������������������  17 Amaia Muñoz-Lopetegi and Carles Gaig

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 Case 5. Multiple Causes for Sleepiness����������������������������������������������������  23 Joan Santamaria

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Case 6. COVID-19, Breathing and Insomnia: There Is More Than One Story����������������������������������������������������������������������������  27 Justa Elizabeth González Naranjo and Juan Enrique Bender del Busto

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 Case 7. Waking Up the Household ����������������������������������������������������������  33 Steve A. Gibbs and Alex Desautels

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 Case 8. “Explosion in My Head is Waking Me Up”��������������������������������  37 Zuzana Belisova

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 Case 9. A Case of Opposites?��������������������������������������������������������������������  39 Rebecca Q. Scott

10 Case  10. Mom Knows Best: No So Transient������������������������������������������  47 Rasik Shah 11 Case  11. Two Faces of the Medallion��������������������������������������������������������  51 Nida F. Tascilar and Carlos H. Schenck 12 Case 12. Watchful Waiting������������������������������������������������������������������������  57 Matthew T. Scharf and R. Nisha Aurora

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Contents

13 Case  13. Measure Twice, Cut Once … or Not at All …��������������������������  61 Boris Chernobilsky 14 Case 14. Snoring Vividly����������������������������������������������������������������������������  65 Andrew J. Westwood 15 Case  15. Central Sleep Apnea and Worsening Headaches ��������������������  69 John G. Park 16 Case  16. “I Am Scared I Will Die from Sleeplessness” ��������������������������  73 Mandana Mahmoudi and Alok Bhatt 17 Case  17. Difficulty Breathing, Difficulty Functioning����������������������������  75 Daniel A. Barone 18 Case  18. “MAD That Stops Breathing” ��������������������������������������������������  79 Saif Mashaqi and Taaha Rafi 19 Case  19. Two for One Isn’t Always Better: When Is a Dual Diagnosis Problematic?����������������������������������������������������������������������������������������������  83 Xinyi Hong, Patrick Sorenson, and Ashura Williams Buckley 20 Case  20. The Mysterious Mustache����������������������������������������������������������  89 Marta Maczaj 21 Case  21. Is There a Link Between Insomnia and Diet?��������������������������  93 Celia Garcia-Malo and Diego Garcia-Borreguero 22 Case  22. Not Your Typical Sleepy Adolescent������������������������������������������  97 Ioanna Kouri 23 Case 23. Sleep Trauma������������������������������������������������������������������������������ 101 Scott Hirsch 24 Case  24. Getting to the Heart of the Matter�������������������������������������������� 105 Nishay Chitkara 25 Case  25. Movements Come in Different Ways���������������������������������������� 109 Montserrat Pujol Sabate 26 Case  26. Sometimes Sleep Hygiene Is Not Just Sleep Hygiene�������������� 113 Rebecca Q. Scott 27 Case 27. Storage Wars ������������������������������������������������������������������������������ 119 Thomas Gustafson and Snigdha Pusalavidyasagar 28 Case  28. Sleeping Up an Appetite ������������������������������������������������������������ 123 Milan Nigam and Steve A. Gibbs 29 Case  29. Not All Sleep Studies Are the Same, Timing and Teaming Are Essential������������������������������������������������������������������������������������������������������ 129 Rasik Shah

Contents

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30 Case  30. Cyclical Insomnia and Hypersomnia���������������������������������������� 133 Alok Bhatt and Mandana Mahmoudi 31 Case  31. Restless Pelvis������������������������������������������������������������������������������ 137 Daniel A. Barone 32 Case  32. A Young Child with Sleep Onset Insomnia and “Weird” Feelings on His Legs ������������������������������������������������������������������ 139 Lourdes M. DelRosso and Raffaele Ferri 33 Case  33. Hallucinations May Be the Clue������������������������������������������������ 145 Alex Iranzo 34 Case  34. Hard to Diagnose, Hard to Treat���������������������������������������������� 149 Akinbolaji Akingbola, David J. Bond, and Snigdha Pusalavidyasagar 35 Case  35. High Pressure Situation�������������������������������������������������������������� 155 Xinyi Hong, Patrick Sorenson, and Ashura Williams Buckley 36 Case  36. A Cerebral Change in Eating Behavior������������������������������������ 159 Nishay Chitkara 37 Case  37. “I’m Not Schizophrenic!” Is It Catalepsy or Cataplexy? ������ 163 Marta Maczaj 38 Case  38. A Sleepy Patient with “Epileptic Seizures” and Disturbed Night Sleep�������������������������������������������������������������������������������� 167 Amaia Muñoz-Lopetegi and Carles Gaig 39 Case  39. Behind the Sleepiness ���������������������������������������������������������������� 173 Sofia Romero-Peralta and Diego Garcia-Borreguero 40 Case  40. All Stress No Rest������������������������������������������������������������������������ 179 Andrew J. Westwood 41 Case  41. Night Terrors Are Not Always What They Seem �������������������� 183 Ewa I. Koziorynska 42 Case  42. Asleep or Not Asleep, That Is the Question������������������������������ 189 Siddhartha S. Nadkarni 43 Case  43. “Somebody Is Standing by My Bed When I Am Falling Asleep”…���������������������������������������������������������������������������������������������������� 193 Zuzana Belisova 44 Case  44. Timing Is Everything������������������������������������������������������������������ 197 Matthew T. Scharf and R. Nisha Aurora 45 Case  45. Lullaby and Goodnight Say Goodbye to These Spikes… ������ 201 Morris H. Scantlebury 46 Case  46. Breathing Is Not the Complete Story���������������������������������������� 207 Alcibiades J. Rodriguez

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47 Case  47. Rapidly Worsening Obstructive Sleep Apnea�������������������������� 213 Boris Chernobilsky 48 Case  48. Unusual Cause of Worsening AHI on CPAP Download���������� 217 John G. Park 49 Case  49. The Therapeutic Labyrinth of Multimorbidity ���������������������� 223 Diego Garcia-Borreguero and Carolina Miranda-Castillo 50 Case  50. My Legs Move When I Lie Down���������������������������������������������� 229 Joan Santamaria 51 Case  51 (Bonus Case). Sleepless Could Be Fatal ������������������������������������ 233 Marta Ros and Gemma Sansa Index�������������������������������������������������������������������������������������������������������������������� 239

Contributors

Akinbolaji  Akingbola, MD, MS  Department of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Minnesota Medical School, Minneapolis, MN, USA R.  Nisha  Aurora, MD, MHS  Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA Daniel A. Barone, MD  Department of Neurology, New York-Presbyterian, Weill Cornell Medicine, New York, NY, USA Zuzana Belisova, MD  Department of Neurology, NYU Langone Medical Center, New York, NY, USA Alok Bhatt, MBBS  Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, NYU Grossman School of Medicine, New York, NY, USA David  J.  Bond, MD, PhD  Department of Psychiatry and Behavioral Sciences, University of Minnesota Medical School, Minneapolis, MN, USA Ashura  Williams  Buckley, MD  National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA Boris Chernobilsky, MD  Otolaryngology—Head and Neck Surgery and Internal Medicine, NYU Langone Health, New York, NY, USA Nishay  Chitkara, MD  Internal Medicine/Pulmonary, Critical Care and Sleep Medicine, NYU Langone Health and Bellevue Hospital, New York, NY, USA Juan  Enrique  Bender  del Busto, MD  Department of Neurology, International Center for Neurological Restoration, La Habana, Cuba Lourdes  M.  DelRosso, MD, MEd  Department of Pediatrics, University of Washington, Seattle, WA, USA Alex Desautels, MD, PhD  Department of Neurosciences, Université de Montréal, Center for Advanced Research in Sleep Medicine, Hôspital du Sacré-Coeur, Montreal, QC, Canada

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Contributors

Hernando Pérez Díaz, MD  Sleep and Epilepsy Program, Centro de Neurología Avanzada, Seville, Spain Raffaele  Ferri, MD  Sleep Research Centre, Oasi Research Institute—IRCCS, Troina, Italy Carles  Gaig, MD, PhD  Department of Neurology, Hospital Clinic Barcelona, Barcelona, Spain Diego Garcia-Borreguero, MD, PhD  Sleep Research Institute, Madrid, Spain Celia Garcia-Malo, MD, PhD  Sleep Research Institute, Madrid, Spain Steve A. Gibbs, MD, MSc  Department of Neurosciences, Université de Montréal, Center for Advanced Research in Sleep Medicine, Hôspital du Sacré-Coeur, Montreal, QC, Canada Madeleine Grigg-Damberger, MD  Department of Neurology, University of New Mexico Medical Center, Albuquerque, NM, USA Thomas  Gustafson, MD  Department of Sleep Medicine, M Health Fairview, Minneapolis, MN, USA Scott Hirsch, MD  NYU Langone Medical Center, Rye Brook, NY, USA Xinyi Hong, BS  National Institutes of Health, Bethesda, MD, USA Alex  Iranzo, MD, PhD  Department of Neurology, Hospital Clinic Barcelona, Barcelona, Spain Ioanna Kouri, MD  Department of Pediatrics, Mitera, Athens, Greece Ewa I. Koziorynska, MD  Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA Marta Maczaj, MD  Sleep Disorders Center, St. Charles Hospital and Rehabilitation Center, Port Jefferson, NY, USA Mandana  Mahmoudi, MD, MPH, PhD  Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, NYU Grossman School of Medicine, New York, NY, USA Saif Mashaqi, MD  Pulmonary, Allergy, Critical Care, and Sleep Medicine, Banner University Medical Center, University of Arizona College of Medicine, Tucson, AZ, USA Carolina Miranda-Castillo, MD  Sleep Research Institute, Madrid, Spain Amaia  Muñoz-Lopetegi, MD  Department of Neurology, Hospital Clinic Barcelona, Barcelona, Spain Susan  Muraida, MD  Internal Medicine, University of New Mexico Hospital, Albuquerque, NM, USA

Contributors

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Siddhartha  S.  Nadkarni, MD  Neurology and Psychiatry, NYU, New York, NY, USA Justa Elizabeth González Naranjo, MD  Clinical Neurophysiology, International Center for Neurological Restoration, La Habana, Cuba Milan Nigam, MD  Department of Neurosciences, Université de Montréal, Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Coeur, Montreal, QC, Canada John  G.  Park, MD  Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA Snigdha  Pusalavidyasagar, MD  Division of Pulmonary, Allergy, Critical Care and Sleep, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA Taaha  Rafi, MD  Sleep Medicine, Banner University Medical Center, Tucson, AZ, USA Alcibiades  J.  Rodriguez, MD  Department of Neurology, NYU Langone Comprehensive Epilepsy Center-Sleep Center, New York, NY, USA Sofia Romero-Peralta, MD  Department of Neurology, Sleep Research Institute, Madrid, Spain Sleep Unit, Pneumology Department, University Hospital of Guadalajara, Guadalajara, Spain Marta  Ros, MD  Department of Neurology, Parc Taulí Hospital Universitari, Sabadell (Barcelona), Spain Montserrat  Pujol  Sabate, MD, PhD  Neurology Service and Multidisciplinary Sleep Unit, Hospital Universitari Santa Maria, Lleida, Spain Gemma  Sansa, MD, PhD  Department of Neurology, Parc Taulí Hospital Universitari, Sabadell (Barcelona), Spain Joan  Santamaria, MD, PhD  Neurology Service, Hospital Clínic of Barcelona, Barcelona, Catalonia, Spain Morris  H.  Scantlebury, MD  Department of Pediatrics, Alberta Children’s Hospital, Calgary, AB, Canada Matthew T. Scharf, MD, PhD  Department of Medicine and Neurology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA Carlos H. Schenck, MD  Department of Psychiatry and Minnesota Regional Sleep Disorders Center, Hennepin County Medical Center and University of Minnesota Medical School, Minneapolis, MN, USA Rebecca Q. Scott, PhD  Department of Neurology, NYU Langone Comprehensive Epilepsy Center-Sleep Center, New York, NY, USA

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Contributors

Rasik Shah, MD  Department of Pediatrics, NYU Grossman School of Medicine, Hassenfeld Children’s Hospital, New York, NY, USA Patrick Sorenson, MA  Sleep and Neurodevelopment Service, National Institute of Mental Health, Bethesda, MD, USA Jordan  C.  Stern, MD  Otolaryngology/Sleep Medicine, BlueSleep, New York, NY, USA Nida F. Tascilar, MD  Department of Neurology and Electroneurophysiology and Sleep Laboratory, Camlica Medipol University Hospital and Istanbul Medipol University Medical School, Istanbul, Turkey Juan  Jesús  Rodríguez  Uranga, MD  Epilepsy Program, Centro de Neurología Avanzada, Seville, Spain Andrew J. Westwood, MD  Department of Neurology, Maidstone and Tunbridge Wells NHS Trust, Kent, UK

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Case 1. The Borderlands of Sleep-Wake Movements and Epilepsy Hernando Pérez Díaz and Juan Jesús Rodríguez Uranga

History A 53-year-old woman was referred for a second medical opinion in 2020 by a colleague. She had originally presented in 2016 with several episodes of complex abnormal movements occurring during sleep and, upon awakening from sleep, but without loss of consciousness. Previously, this had been diagnosed as a drug-­ refractory epilepsy. My colleague ordered video-EEG monitoring (see report), which registered a total of 23 paroxysmal episodes of complex motor semiology that occurred both during sleep, upon awakenings and the wake period in the daytime. There was no associated change in the electroencephalogram (EEG) activity and no interictal epileptiform discharges. The patient reports that she can have up to 6 episodes per night, lasting between 5 and 15 s each time and that they can occur at any time of the night [according to a 2020 video-EEG-polysomnography (PSG), she underestimated the frequency and duration of episodes (see report)]. During the episodes, the patient can speak “with difficulty”. These episodes started around age 2. Until approximately age 50, they occurred mainly during sleep with rare events during wakefulness. After age 50, they could happen during the day, but only after awakening from a nap. There are no triggers for these events. Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/978-­3-­031-­18374-­4_1. H. P. Díaz (*) Sleep and Epilepsy Program, Centro de Neurología Avanzada, Seville, Spain J. J. R. Uranga Epilepsy Program, Centro de Neurología Avanzada, Seville, Spain © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 A. J. Rodriguez (ed.), Sleepless and Sleepy, https://doi.org/10.1007/978-3-031-18374-4_1

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She does snore and frequently has problems with falling and staying asleep. During the day, the patient feels extremely tired and has complaints of neck, arm and knee pain. For these events, the patient has previously trialed (alone or in combination) carbamazepine, levetiracetam, valproic acid, diazepam, amitriptyline, clobazam, oxcarbazepine (worsened symptoms), quetiapine, perampanel and mirtazapine—all with no response to treatment. She does note that she sleeps a bit better with 100 mg of trazodone nightly, but the episodes persist. The patient started to walk at around age 2, but there were no other developmental issues. There is no family history of movement disorders or epilepsy.

Examination Normal general and neurological examination.

Investigations 3-Tesla brain magnetic resonance imaging (MRI): normal. Video-EEG monitoring 2016: EEG background activity within normal range. Interictal EEG: no interictal epileptiform abnormalities. A total of 23 episodes are recorded, both during the wake period and during the night on waking up, with a complex motor semiology with no change in consciousness, which has no effect on EEG activity. Video EEG-polysomnography (2020): There were 12 events consisting of choreoathetosis and ballistic movements with no loss of consciousness, lasting an average of 30 s and occurring during NREM sleep stages. Due to these clinical manifestations, the episodes were very suggestive of paroxysmal hypnogenic dyskinesia. There was no sleep disordered breathing or periodic limb movement of sleep observed. REM sleep stage had normal muscle atonia. Description of one of these events (see Video 1.1): the patient started with right hand flickering movement, then both legs extended, followed by flexion of legs, turning her body to the right side, truncal extension, arm stretching and semi-­purposeful movement of hands reaching out to her body as if she is picking on her clothes. It subsided in 50 s and she had only occasional feet flexion. Home video (not included) showed similar movements and extension of trunk, flexion of legs, arms folded around her chest in a brief period without opening eyes. She woke up after one episode. Genetic study: mutation c.640G.C (p.Ala214Pro) in gene PRRT2.

1  Case 1. The Borderlands of Sleep-Wake Movements and Epilepsy

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Diagnosis PAROXYSMAL HYPNOGENIC DYSKINESIA

Discussion Paroxysmal dyskinesias are defined as a heterogeneous group of syndromes characterized by recurring episodes of sudden onset involuntary movements of an intermittent or episodic nature without associated loss of consciousness. Abnormal movements are primarily dystonia and/or chorea, and to a lesser extent ballismus or athetosis, but do not include tremor or myoclonus. The following movement disorders differ based on their triggers and duration: paroxysmal kinesigenic dyskinesia (PKD), paroxysmal nonkinesigenic dyskinesia (PNKD), paroxysmal exertion-induced dyskinesia (PED), and paroxysmal hypnogenic dyskinesia (PHD) [1]. PHD is a disease that is likely underdiagnosed and often confused with sleep-­ related hypermotor epilepsy. In our experience, it is not rare for some of the patients treated for this disease in our unit to be referred with the diagnosis of refractory epilepsy on various anti-seizure medications (ASMs) with no improvement, although the literature indicates responses to ASMs due to the still confusing distinction and overlap that exists between both disorders. This disorder normally starts during adolescence (range 2–47 years of age) and shows no sex predominance. The trigger for PHD is non-REM sleep. The literature indicates average episode durations of 30–45 s and average frequencies of between 5 episodes per year to up to 5 episodes per night; however, in our experience, episodes can last as long as 2–5 min and the patient may suffer frequencies in excess of 20 episodes per night [1]. In its primary form, PHD is a channelopathy and is associated with two genes: –– PRRT2 -c.649dupC- for which over 70 mutations have been identified (95% nonsense or frameshift) and which is mainly associated with PKD, but also with the other 3 forms of paroxysmal dyskinesia as its transmission is autosomal dominant. Syndromic signs and symptoms usually start before the age of 18 years. It is also associated with infantile convulsions and choreoathetosis, benign familial infantile seizures, migraines, familial hemiplegic migraine, episodic ataxia, childhood absence epilepsy, febrile seizures, and benign paroxysmal torticollis. In homozygosity, it can lead to intellectual disability (to a greater or lesser degree), persistence of the paroxysmal episodes and prolonged ataxia episodes [2]. The PRRT2 protein is ubiquitously located in the neocortex, hippocampus, basal ganglia and cerebellum, which anatomically correlate with the range of clinical symptoms. PRRT2 interacts with the synaptosomal-associated protein 25 (SNAP25) in glutamatergic synapses. SNAP25 is a presynaptic membrane protein that allows for fusion of synaptic vesicles and calcium-mediated neuronal exocytosis in order to modulate glutamate release. In PRRT2 mutations, the PRRT2 protein changes its usual location from the membrane to the cytoplasm,

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interacts with SNAP25, alters the properties of the calcium voltage-dependent channel Cav2.1, and therefore enhances intracellular glutamate levels leading to neuronal hyperexcitability. Otherwise, PRRT2 expression increases during the development and is correlated to neuronal migration and synaptic density. This explains why biallelic PPRT2 mutations can result in neurodevelopmental disorders [1, 2]. –– ADCY5 is fundamentally associated with PHD, and to a lesser extent PKD and PNKD, which are also autosomal dominant. It has been associated with alternating hemiplegia of childhood, axial hypotonia, nonparoxysmal dystonia and chorea. ADCY5 gene encodes for adenylate cyclase 5, which is strongly expressed in the striatum and converts adenosine triphosphate to 3′,5′-cyclic adenosine monophosphate and pyrophosphate. ADCY5 integrates signals from adenosine A2A, D1 and D2 dopamine receptors, among others. ADCY5 mutation carriers display a broad phenotypic spectrum with a genotype–phenotype correlation. The most common mutation, p.Arg418Trp, presents with a more severe phenotype than that of p.Arg418Gln and p.Ala726Thr. These mutations likely increase adenylate cyclase activity, thereby distinctly affecting signal transduction in the striatum [1]. ADCY5 patients typically show onset of signs during childhood with a mixture of persistent hyperkinetic movements (chorea, dystonia or myoclonus) characterized by: axial hypotonia, orofacial jerks (not true myokymia), sleeprelated paroxysmal dyskinesia and painful paroxysmal dyskinesia. They have marked fluctuations in frequency and severity of movements without seizures, ataxia or marked cognitive impairment. They have normal brain MRI scans and stable or very slow progression of symptoms. Attacks of paroxysmal dyskinesia last for minutes with discrete onset and offset, waxing and waning over the course of weeks to months. This pattern makes it difficult to distinguish triggers or response to medications. In fact, the combination of multiple paroxysmal dyskinesia subtypes (e.g., PKD, PNKD and PHD) or paroxysmal dyskinesia that do not fit clearly into previous defined paroxysmal dyskinesia categories are clues to suspect ADCY5 mutations [1]. Patients with PHD are usually referred as refractory epilepsy and there are patients with an overlap between epileptic seizures and PHD episodes, so it is difficult to know where the limits are. However, in PHD the movements—dystonia, chorea, ballismus and/or athetosis—seem to have a subcortical origin, are intrinsically anarchic and non-stereotyped, the consciousness is maintained, and the duration of the episodes is longer than in the epileptic seizures. The differential diagnosis of paroxysmal events during sleep must include PHD, which may help for faster work up, diagnosis and therapeutic intervention. Acknowledgment  The authors wish to thank Professor Un Jun Kang, MD, director of translational research at the Fresco Institute for Parkinson’s disease and movement disorders at NYU Langone Medical Center for his suggestions reviewing the case presentation and video.

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References 1. Manso-Calderon R.  The spectrum of paroxysmal dyskinesias. Future Neurol. 2019;14(3):FNL26. 2. Liu XR, Huang D, Wang J, Wang YF, Sun H, Tang B, et al. Paroxysmal hypnogenic dyskinesia is associated with mutations in the PRRT2 gene. Neurol Genet. 2016;2(2):e66. https://doi. org/10.1212/NXG.0000000000000066. PMID: 27123484; PMCID: PMC4830198.

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Case 2. Sometimes Lightheadedness a Harbinger Susan Muraida and Madeleine Grigg-Damberger

History Determined to join her school pep squad practicing long and hard, a 13-year-old girl began complaining of episodes of awakening feeling nervous and lightheaded, especially when awakened by her new loud alarm clock. One night resting in bed, she ran from the room complaining of chest pain and shortness of breath. She saw her pediatrician who examined her and said it was “just stress.” One week later, awakened by her alarm clock, she had a generalized convulsion followed by a cardiac arrest. Parents performed cardiopulmonary resuscitation. She took no medications, had no significant past medical history, and used no recreational drugs.

S. Muraida (*) Internal Medicine, University of New Mexico Hospital, Albuquerque, NM, USA e-mail: [email protected] M. Grigg-Damberger Department of Neurology, University of New Mexico Medical Center, Albuquerque, NM, USA e-mail: [email protected] © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 A. J. Rodriguez (ed.), Sleepless and Sleepy, https://doi.org/10.1007/978-3-031-18374-4_2

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Examination Paramedics arrived and patient was successfully resuscitated. Exam following successful cardiac conversion showed: blood pressure 102/60 mmHg, pulse rate 65 beats per minute, respiratory rate 16, pulse oximetry 96%, body mass index (BMI) 17 kg/m2. Patient appeared well-nourished. Cardiac, pulmonary, and neurological exams were normal.

Investigations Point-of-care glucose was 85. Complete metabolic panel showed normal potassium, magnesium, and calcium. Post-conversion she was found to have an abnormal EKG showing alternating T waves. A 12-lead electrocardiogram (EKG) was performed at the hospital and found to be abnormal (shown in Fig. 2.1).

Fig. 2.1  EKG shows a prolonged QT interval of 544 ms (QTc interval corrected for the heart rate 647 ms). Notched T waves noted in leads II, III, aVF, and V1–V6

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Differential Diagnosis Brugada syndrome, cardiac syncope; convulsive syncope; hypertrophy cardiomyopathy, long QT syndrome.

Discussion and Management Syncope, seizure, cardiac arrest or death awakened by an alarm clock warrants consideration of congenital long QT syndrome (LQTS) type 2. The EKG showed prolonged QTc interval of 647 ms and notched T waves. Genetic testing showed she had a loss of function mutation in the hERG (KCNH2) cardiac potassium channel gene (LQTS type 2). Congenital LQTS (c-LQTS) is a disorder of ventricular myocardial repolarization characterized by a prolonged QT interval on the EKG which can lead to torsades de pointes (TdP), sudden cardiac arrest, and sudden cardiac death [1, 2]. LQTS can be congenital or acquired. Congenital LQTS (c-LQTS) has a prevalence of 1  in 2000 live births. Mutations in three cardiac ion channel genes account for 80% of c-LQTS cases: KCNQ1 (LQT1); KCNH2 (LQT2); and SCN5A (LQT3). The congenital form typically presents in the first two decades. The initial symptom (most often between ages 8 and 10 years) is syncope in 69%; cardiac death in 10–13%. c-LQTS cause 3000–4000 sudden deaths children and young adults each year in the United States. Patients during LQTS cardiac events often report palpitations, lightheadedness, dizziness, near-syncope and/or syncope. TdP can be a transient short self-limited arrhythmia but when longer and/or evolving to ventricular fibrillation can lead to cardiac arrest and cardiac death. When cardiac output decreases significantly during non-sustained episodes of TdP it leads to cerebral hypoperfusion sufficient to cause syncope and/or seizures. LQTS cardiac events are often triggered by specific triggers which vary with the specific LQTS genotype (summarized in Fig. 2.2). Patients with LQT2 (our patient) typically have LQT cardiac events triggered by sleep, rest or auditory stimuli (such as an alarm clock, telephone ringing, thunderbolt, or baby crying). In one case series of 670 patients with c-LQTS, a lethal event in 110 was provoked by a specific trigger. In LQT1 patients, 90% events occurred during a particularly emotional event or exercise (especially while swimming). LQT events occurred during sleep or rest in 80% with LQT3, 63% in LQT2. Eighty percent of events in LQT3 occurred at sleep/ rest; arousal 80% LQT3, 63% LQT2. Night rest lengthens PR and QT intervals, and prolongs QRS. TdP is the classic cardiac arrhythmia associated with LQTS in which peaks of the QRS complexes twist around an isoelectric line of the EKG tracing. TdP episodes are usually brief and end spontaneously. However, patients may experience multiple episodes of the arrhythmia, and episodes can recur in rapid succession and may induce syncope or progress to ventricular fibrillation. A markedly prolonged

37% sudden loud noises, acute arousals, or emotions;

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Cardiac events more lethal, tend to have marked resting bradycardia and arrhythmias bradycardia related.

63% sleep or rest;

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15% exercise; 5% emotions;

Estrogen may affect potassium channel function → longer QTc.

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Testosterone shortens QT interval;

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Adolescent boys more events girls;

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80% sleep, rest, night;

15% emotional stress;

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75% exercise (especially swimming);

Triggers for Sudden Death

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Fig. 2.2  Most common congenital long QT syndrome phenotypes

10% of all mutations

Gain of function in cardiac sodium channel gene SCN5A

LQT3

40% of all mutations

Loss of function in hERG (KCNH2) cardiac potassium channel gene

LQT2

40% of all mutations

Loss of function in KCNQ1 cardiac potassium channel gene

LQT1

LQTS Type, Genotype, Gene Mutation and Effect

T-wave morphology

10 S. Muraida and M. Grigg-Damberger

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QT interval precedes the onset of TdP; the ventricular rate 160–250  beats/min, irregular R-R intervals, and cycling of the QRS axis 180° every 5–20 beats. Bradycardia is usually associated with TdP in acquired LQTS, whereas catecholamine surges trigger TdP in c-LQTS. Acquired LQTS is far more common than c-LQTS, and is most often triggered by QT-interval prolonging drugs or electrolyte disturbances (hypokalemia, hypomagnesemia, hypocalcemia, starvation, liquid protein diets, and anorexia nervosa) or cocaine. Twenty percent of patients with symptomatic acquired LQTS have subclinical LQTS mutations. The importance of a good history to identify LQTS before it is lethal cannot be understated. Clinicians should explore situational factors that trigger syncopal symptoms, obtain a thorough history of medications, substance use and family history of unexplained sudden death